It has been demonstrated that CD8-positive CTLs recognize epitope peptides derived from tumor-associated antigens (TAAs) on the major histocompatibility complex (MHC) class 1 molecule, and then kill the tumor cells. Since the discovery of melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered through immunological approaches (NPLs 1, 2), and some of these TAAs are now in the process of clinical development as immunotherapeutic targets.
Favorable TAA is indispensable for proliferation and survival of cancer cells, as a target for immunotherapy, because the use of such TAAs may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses warrants further development and thus clinical application of peptide vaccination strategies for various types of cancer is ongoing (NPLs 3 to 10). To date, several clinical trials using these TAA derived peptides have been reported. Unfortunately, many of the current cancer vaccine trials have shown only a low objective response rate (NPLs 11 to 13). Accordingly, there remains a need for new TAAs as immunotherapeutic targets.
The TOMM34 gene (GenBank Accession No. NM—006809), translocase of outer mitochondrial membrane 34, has been identified from human EST and cDNA databases and predicted to encode a protein containing degenerated tetratricopeptide repeat (TPR) motifs (NPL 14). The protein encoded by this gene is involved in the import of precursor proteins into mitochondria. This protein has a chaperone-like activity, binding the mature portion of unfolded proteins and aiding their import into mitochondria (NPL 15).
In a recent study, it was indicated that TOMM34 is frequently up-regulated in colorectal cancer by gene-expression profile analysis using cDNA microarray consisting of 23040 genes. Furthermore, knockdown of TOMM34 by siRNA in colon cancer cell lines attenuated the growth of colon cancer cells (NPL 16).